Author: Shana L Johnson MD, AskDrShana


There are multiple classes of medications that lower the reactivity and pain signals from nerves. Many of the medications were developed for other medical conditions but were found to reduce nerve pain. I refer to them as “neuropathic agents” since they lower reactivity and pain signaling from the nerves. Neuropathic agents turn down the volume of the pain. For example, if someone experiences 9/10 nerve pain, a nerve pain agent may “turn down” the pain level to a 4/10.


Common Medications for Sensitization and Nerve Pain

There are 3 main classes of neuropathic agents that are used first-line. They include the tricyclics, anticonvulsants, and SNRIs.

Anticonvulsants– commonly used examples–gabapentin, pregabalin, lamotrigine, oxcarbazepine

Tricyclics– commonly used examples– amitriptyline, nortriptyline

SNRIs (serotonin and norepinephrine reuptake inhibitors)–examples– duloxetine, venlafaxine


Although FDA labeled for different medical conditions than nerve pain, they have all been found to be helpful in treating neuropathic pain. Each class lowers nerve pain through a different mechanism. Since they use different mechanisms, for severe pain, two medications from two different classes targets the pain from different angles. Which medication class works best for an individual depends on the person and the other symptoms they have. For example, if someone has nerve pain and can’t sleep at night, a medication that calms pain signals and aides sleep is a good fit. The anticonvulsant class and the tricyclic class both help with nerve pain and sleep. Alternatively, if there is nerve pain and major depression, the SNRI class treats both conditions.



The first class of medications is the anticonvulsant class. These are medications that are FDA labeled for seizures but work well for nerve pain. Much akin to how seizure medications lower nerve excitability to reduce seizures, they also lower excitability to reduce pain signals. Common examples in this group include gabapentin and pregabalin. Although FDA labeled for seizures, gabapentin and pregabalin are really better suited for treating nerve pain. This class is commonly the first-line medical therapy for acute nerve pain, like sciatica or pinched nerves. This class is effective for chronic nerve pain as well including pain arising from sensitization syndromes. For harder-to-treat cases or if another agent is considered, oxcarbazepine and lamotrigine are options as well.

Gabapentin is user-friendly since it can be titrated from very low doses to very high doses; you can tailor it to the individual. Titrating the dose to the individual is key to successful treatment of nerve pain. Everyone has their own effective dose. Some need only low doses for relief, while others need much higher doses. Gababpentin allows for this titration. Pregabalin is effective but less room to titrate to the individual.

The most common reason I saw people with ineffective nerve pain control was because of inadequate titration of the nerve pain agent being used. For example, Joan was given gabapentin 100mg and was miserable with her sciatic nerve pain. We increased her dose to 300mg and her nerve pain level decreased to 2/10 and she felt much better. It wasn’t that the medication did not work for her, the issue was her dose was not adjusted to her needs.



The second class of nerve pain medications is the tricyclics. Examples include amitriptyline and nortriptyline. They have been around for 60 years! They are cheap and really effective at low doses. Although FDA labeled for depression, their use today is more for nerve pain. They are rarely used to treat depression anymore. Off-label use is common for many of the sensitization syndromes including chronic low back pain and chronic headaches. They are also helpful for sleep. They are a nice choice if nerve pain is interfering with sleep at night. Since nerve pain often worsens at night, these nighttime nerve medications that also help with sleep are a solid option. They do have side effects that limit their use. In particular, they are not a good class for those who have heart disease or multiple medical issues.


SNRI-Serotonin and Norepinephrine acting

The third class are the SNRI class. A common example is duloxetine. It is FDA labeled for the treatment of various types of chronic pain, depression, and anxiety. This class is a good choice if the person needs treatment for depression, anxiety, and nerve pain. Venlafaxine is also in this class and should theoretically help with nerve pain, however, I didn’t see much efficacy with venlafaxine for nerve pain. For this reason, the main SNRI I used was duloxetine.


Other Nerve Pain Agents

Another medical category with benefit for nerve pain includes cannabis and cannabinoids. When I worked in the multiple sclerosis clinic, many patients found cannabinoids helpful for nerve pain. It also helped with muscle spasms and sleep initiation. Using cannabinoids before bed was a common regimen. There are some topical medications as well, including lidocaine patches and capsaicin patches. A few multiple sclerosis patients found the lidocaine patches helpful for severe nerve pain in their legs and feet.

There are some over-the-counter supplements with potential benefits. The data for efficacy is a bit underwhelming, but worth considering.

Alpha-lipoic acid (Diabetes Care. 2011: 34(9).2054-60)
Acetyl-L-carnitine (Diabetes Care. 2005:28:89-94)


Ketamine has received increased attention in recent years for the treatment of chronic neuropathic pain and treatment-resistant depression. The most efficacy is in pure forms of nerve pain such as spinal cord injury and complex regional pain syndrome. For consideration of ketamine, a specialist consultation is needed. At high doses ketamine works as an anesthetic agent, thus you want someone specialized and knowledgeable in its use!  (Cohen SP.  Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018 Jul; 43(5): 521-546.)

A newer class, nerve growth factor inhibitors, are also under study, such as fasinumab.


Bottom line

Sometimes you need some help from medication therapy. There are many medical options with decades of safety data. The options do need to be specifically tailored to the person. Both the choice of medical therapy and the dosing. Although there is a frustrating trial and error period with nerve pain agents, finding the right combination can greatly reduce suffering.